A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma
We present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (<i>KIF5B</i>)-<i>NTRK1</i> gene fusion that responds well to entrectinib. Moreover, <i>KIF5B</i>-<i>NTRK1</i> gene chimera has been shown to be an oncogene,...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
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| Series: | Current Oncology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1718-7729/31/11/489 |
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| Summary: | We present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (<i>KIF5B</i>)-<i>NTRK1</i> gene fusion that responds well to entrectinib. Moreover, <i>KIF5B</i>-<i>NTRK1</i> gene chimera has been shown to be an oncogene, activating both the MAPK and PI3K/AKT signaling pathways. The biopsy sample was analyzed using various methods such as hematoxylin–eosin staining (HE), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) based on a 1267-gene panel. Additionally, human lung adenocarcinoma cell lines A549 and H1755 were used to obtain a stable expression of chimera gene products. The cell proliferation was confirmed using CCK8 and adhesion-dependent colony formation assay. Cell invasion was confirmed using the transwell invasion assay. The protein levels of the MAPK and PI3K/AKT signaling pathways were assessed using Western blotting. The patient, a 66-year-old Chinese male, was diagnosed with adenocarcinoma (stage IVB) located in the upper lobe of the left lung. NGS analysis identified a novel <i>KIF5B</i>-<i>NTRK1</i> fusion gene, which was further confirmed by FISH and IHC analyses. As a first-line therapy, entrectinib was administered to the patient at a dose of 600 mg once daily, resulting in a partial response. The patient’s progression-free survival (PFS) has now been more than 12 months, and no serious toxicities have been observed so far. Furthermore, stable KIF5B-NTRK1-expressing cells were generated and the experimental results demonstrate enhanced proliferation abilities, along with increased levels of proteins involved in the MAPK and PI3K/AKT signaling pathways. Our study reports a novel <i>KIF5B</i>-<i>NTRK1</i> genetic rearrangement that supports favorable responses to entrectinib. Moreover, in vitro experiments showed that the fusion gene could exert oncogenic properties by activating the MAPK and PI3K/AKT signaling pathways. To summarize, our findings broaden the spectrum of <i>NTRK</i> gene fusions in the context of lung adenocarcinoma. |
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| ISSN: | 1198-0052 1718-7729 |